Drug-Resistance inMycobacterium Tuberculosis:Molecular Basis and Genotypic Detection

Emergence of multidrug-resistant Mycobacterium tuberculosis strains and their global dissemination necessitate development, evaluation and comparison of the rapid molecular tests that target genetic determinants of bacterial drug resistance. A wide range of such methods is available at present and the choice of those most appropriate is among the pertinent tasks of the National Tuberculosis Control Programs. Inadequate and/or interrupted therapy allows the selection of spontaneous mutations in favor of resistant organisms while sequential acquisition of these mutations in different genome loci results in the development of resistance to multiple drugs. The standard DOTS course comprises the five first-line drugs: rifampin (RIF), isoniazid (INH), streptomycin (STR), ethambutol (EMB), and pyrazinamide (PZA). Multi-drug resistance (MDR) is defined as resistance to at least RIF and INH. Anti-TB drug resistance is characterized by multigenic (rpoB, katG, inhA, ndh, embB, rpsL, rrs, pncA, gyrA) control and geographic variation of resistance mutations. Correct and rapid detection of drug resistance facilitates the appropriate and timely delivery of anti-TB therapy and reduces overall treatment cost. The prediction of drug resistance of M. tuberculosis by molecular tools presents a rapid alternative to the culture-based phenotypic susceptibility tests. Among the genotypic methods used to date are direct sequencing, microchips technology, PCR-single strand conformation polymorphism, RNA/RNA mismatch, molecular beacons and other assays. Genotypic methods allow rapid prediction of resistance to main anti- TB drugs in the considerable proportion of M. tuberculosis strains circulating in areas with high burden of MDR-TB.